What DOAC reversal agents can I use?
Non-specific agents
- In the setting of life-threatening bleeding due to factor Xa inhibitors, a dose of Prothrombin Complex Concentrates (PCC) 2000 IU was shown to have good hemostatic effectiveness in nearly 70% of patients
- PCCs are thought to mitigate anti-Xa effect by increasing levels of non-activated clotting factors
- Adjunct therapies like tranexamic acid or topical hemostatic agents can be used to help manage DOAC-associated bleeding, but these are not DOAC reversal agents
Specific DOAC reversal agents
A "reversal agent" implies the presence of a specific antidote to counteract the effects of a drug
|
Direct Thrombin Inhibitor: Dabigatran |
Factor Xa Inhibitors: Apixaban, Edoxaban, Rivaroxaban |
Reversal Agent |
Idarucizumab |
Andexanet alfa |
Health Canada Approved |
Yes |
No |
US FDA Approved |
Yes |
Yes |
EU EMA Approved |
Yes |
Yes |
Indication |
Adult patients treated with dabigatran requiring reversal of anticoagulation for emergency surgery/urgent procedures or life-threatening or uncontrolled bleeding |
Patients treated with apixaban or rivaroxaban requiring reversal of anticoagulation for life-threatening or uncontrolled bleeding (not yet indicated for edoxaban-treated patients) |
Mechanism |
Specific humanized monoclonal antibody fragment against dabigatran |
Recombinant modified human factor Xa protein against factor Xa inhibitors |
Dose |
5 g IV (2 x 2.5 g vials) |
Low Dose: 400 mg IV bolus at a target rate of 30 mg/min, followed by 4 mg/min IV infusion for up to 120 minutes (480 mg) High Dose: 800 mg IV bolus at a target rate of 30 mg/min, followed by 8 mg/min IV infusion for up to 120 minutes (960 mg) See the below chart to determine andexanet alfa dosing based on the specific factor Xa inhibitor dose (timing of factor Xa inhibitor last dose before andexanet alfa initiation) |
Time of Onset |
Immediate |
Immediate |
Andexanet alfa dose based on the specific factor Xa inhibitor dose (timing of factor Xa inhibitor last dose before andexanet alfa initiation):
Last Dose |
<8 Hours or Unknown |
≥8 Hours |
|
Apixaban |
≤10 mg |
Low dose |
Low Dose |
>10 mg or unknown |
High dose |
||
Rivaroxaban |
≤5 mg |
Low dose |
|
>5 mg or unknown |
High dose |
||
Edoxaban (off-label) |
≤30 mg |
Lose dose |
|
>30 mg |
High dose |
References:
- Andexxa® (Andexanet alfa) Package Insert. San Francisco, CA, USA; Portola Pharmaceuticals Inc. December 2018.
- Praxbind® (Idarucizumab) Product Monograph. Burlington, Ontario; Boehringer Ingelheim Canada Ltd. April 18, 2019.
- Carpenter E, Singh D, Dietrich E, et al. Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation. Ther Adv Drug Saf. 2019;10:2042098619888133.
- Hoffman M, Goldstein JN, Levy JH. The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review. Int J Emerg. 2018;11:55.
- Majeed A, Ågren A, Holmström M, et al. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017;130:1706-1712.
- Schulman S, Gross PL, Ritchie B, et al. Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost. 2018;118:842-851.